In this study, we firstly discovered that (1) TMEM211 was highly expressed in tumor tissues and upregulated TMEM211 was associated with shorter PFIS and DSS in colon cancer patients; (2) migration/invasion abilities were reduced and there was deregulated expression of EMT markers in TMEM211-silenced colon cancer cells; (3) the high co-expression of TMEM211/EMT markers in colon cancer cells indicated their correlation with poor DSS in colon cancer patients; and (4) TMEM211 should regulate ERK, AKT and NF-κB signaling pathways in colon cancer cells. This evidence concerns the gene NFKB1 and malignant colon neoplasm.